不同基原秦皮、香豆素单体抗菌作用对比研究

目的研究4种基原秦皮提取物、5种香豆素单体、5种单体混合物、苦枥白蜡树树皮已知香豆素指纹区样品、未知成分指纹区样品的体外抑菌作用。方法采用体外抑菌试验微量定量检测方法，测定最小抑菌浓度及最低杀菌浓度。结果4种基原秦皮苦枥白腊树、尖叶白腊树、白腊树、宿柱白腊树树皮均有明显抑菌、杀菌作用，抑菌强度依次为：宿柱白腊树〉苦枥白腊树〉尖叶白腊树〉白腊树。5种香豆素单体秦皮素、秦皮乙素对9种细菌均有明显抑菌、杀菌作用，秦皮甲素、秦皮苷对金黄色葡萄球菌、表皮葡萄球菌有一定抑菌、杀菌作用，抑菌作用依次为：秦皮素〉秦皮乙素〉秦皮甲素〉秦皮苷〉6，7-二甲氧基-8-羟基香豆素。苦枥白腊树树皮提取物对所试9种细菌均有明显抑菌作用；单体混合物，已知香豆素指纹区样品对金黄色葡萄球菌、表皮葡萄球菌、乙型溶血性链球菌、绿脓杆菌、大肠杆菌、肺炎克雷伯氏菌、卡他菌有明显抑菌作用；未知成分指纹区样品对金黄色葡萄球菌有明显抑菌作用，对表皮葡萄球菌、甲型溶血性链球菌、乙型溶血性链球菌、大肠杆菌、沙门氏菌也有一定抑菌作用。结论秦皮抑菌强弱与已知香豆素成分含量高低基本一致。秦皮中苷元的抑菌作用优于苷，5种香豆素类单体中秦皮素、秦皮乙素抑菌作用最强。     

石椒草化学成分研究

采用硅胶、ODS、Sephadex LH-20和制备型高效液相等色谱方法对石椒草属植物石椒草Boenninghausenia sessilicarpa全草乙醇提取物的石油醚萃取部位进行分离纯化,同时根据化合物波谱数据对单体化合物进行结构鉴定。从石油醚萃取部位共分离鉴定了15个香豆素类化合物,结构鉴定分别为：欧芹烯酮酚甲醚（1）、九里香素（2）、3-(1,1-二甲基烯丙基)-8-羟基-7-甲氧基香豆素（3）、花椒毒素（4）、异茴芹素（5）、状芸香素（6）、异去甲基呋喃羽叶芸香素（7）、欧前胡素（8）、珊瑚菜内脂（9）、白芷脑素（10）、白当归素（11）、新比克白芷内酯（12）、chalepin(13)、鲁望桔内酯（14）、3-(1,1-二甲基烯丙基)-花椒内酯（15）。化合物1～3、6～10和14～15均首次从石椒草中分离得到。     

东北鹤虱中香豆素类对兔离体回肠的作用

目的：观察东北鹤虱中香豆素类对兔离体回肠的作用及对钙离子的影响。方法：采用兔离体回肠标本，结予不同剂量香豆素（CM）及维拉帕米（Ver)，观察对平滑肌收缩的影响。结果：CM和Ver可剂量依赖性地抑制乙酰胆碱（Ach）引起的回肠的收缩，非竞争性拮抗Cacl2所致回肠收缩，并对Ach引起的第1，2相收缩有影响。结论：东北鹤虱中提取的香豆素类具有与Ver相似的钙拮抗作用。     

秦皮总香豆素致突变作用研究

目的评价秦皮总香豆素的致突变性。方法应用Ames试验、小鼠骨髓微核试验对秦皮总香豆素进行了致突变研究。结果秦皮总香豆素在受试剂量40～20000μg/皿范围内,各剂量组各菌株与阴性对照组比较均未见回变菌落数明显增加。秦皮总香豆素三个试验剂量组微核率均在正常范围内,经卡方检验与阴性对照组比较无显著性差异(P>0.05)。结论本实验条件下秦皮总香豆素无致突变作用。     

Heparin-Induced Thrombocytopenia and Vascular Surgery

Heparin-induced thrombocytopenia (HIT) is of special interest to vascular surgeons as heparin is the predominant anticoagulant used before, during, and after vascular surgery. Further, the prothrombotic nature of this antibody-mediated disorder leads to a high frequency of limb ischemia due to large arterial occlusion by platelet-rich (“white”) clots or because of extensive venous thrombosis involving large veins and small venules. This latter syndrome has been associated with coumarin anticoagulation of HIT-associated deep-vein thrombosis (coumarin-induced venous limb gangrene). Non-heparin anticoagulants, such as the direct thrombin inhibitors (lepirudin, argatroban), may be needed for intraoperative management of a patient with suspected acute HIT who requires vascular surgery. The transience of HIT antibodies provides a rationale for intraoperative use of heparin in a patient who has recovered from HIT and in whom HIT antibodies are no longer detectable.     

Evaluation of Coumarin and Neoflavone Derivatives as HCV NS5B Polymerase Inhibitors

Coumarins and coumestans represent an important family of compounds with diverse pharmacological properties. We recently identified coumestans as novel inhibitors of hepatitis C virus NS5B polymerase and predicted their binding in thumb pocket‐1 (TP‐1) of NS5B. As the coumarins are structurally related to coumestans by virtue of their common A‐ and B‐rings, we postulated them to also exhibit similar binding interaction with NS5B and inhibit its polymerase function. We therefore investigated 24 coumarin and neoflavone derivatives as candidate NS5B inhibitors and identified 14 compounds inhibiting NS5B polymerase activity with IC₅₀ values between 17 and 63 μm . Of these, the newly synthesized 6,8‐diallyl‐5,7‐dihydroxycoumarin ( 8a ) was produced in three steps in high chemical yield from floroglucinol and found to be the most potent of this series, exhibiting activity similar to the reference coumestan LQB‐ 34 . The binding site of 8a was mapped to TP‐1 of NS5B by counter screening against P495L NS5B mutant, employed as a screen for TP‐1 site binders. NS5B‐TP‐1‐ 8a interaction map provided insight into 8a binding and offered clues for future SAR optimization.     

Anti-inflammatory and antimicrobial coumarins from the stems of Eurya chinensis

Two new coumarins, named (±)-euryacoumarin A (1) and 6-demethylobtusinin (2), and one new natural coumarin, named euryacoumarin B (3), along with two known compounds, scopoletin (4) and obtusinol (5), were isolated from the stems of Eurya chinensis. Their structures were elucidated by means of extensive spectroscopic methods and comparison with data reported in the literatures. Compound 1 exhibited significant inhibition of LPS-induced nitric oxide (NO) production in RAW264.7 cells with IC₅₀ value of 35.64 ± 1.73 μM, and showed marginal antibacterial activities against Bacillus subtilis and B. cereus with MIC values of 50.59 ± 2.12 and 35.42 ± 0.96 μM, respectively.     

雷公藤内酯醇的细胞内定位研究?

目的：检测雷公藤内酯醇的细胞内定位,探讨其在细胞内的作用位点。方法采用4-溴甲基-7-甲氧基香豆素标记雷公藤内酯醇,与人肝癌细胞孵育;并与细胞核染料 PI 或细胞质膜染料 DiI 行双色荧光染色,用荧光显微镜观察。结果与对照相比,香豆素标记在紫外激发下呈特异性的淡蓝色荧光;与 DiI 共定位显示,香豆素标记在细胞质(膜)存在;与 PI 共定位显示,香豆素标记在细胞核存在,且荧光强于细胞质(膜)。结论雷公藤内酯醇在细胞内主要位于细胞核,其次是细胞质(膜),提示雷公藤内酯醇可能主要在细胞核内起作用,其次是在细胞质(膜)上起作用。     

Inhibition of Mild Steel Corrosion in Hydrochloric Acid Solution by New Coumarin

A new coumarin derivative, N,N′-((2E,2′E)-2,2′-(1,4-phenylenebis(methanylylidene))bis(hydrazinecarbonothioyl))bis(2-oxo-2H-chromene-3-carboxamide) PMBH, was synthesized and its chemical structure was elucidated and confirmed using spectroscopic techniques (Infrared spectroscopy IR, Proton nuclear magnetic resonance, ¹H-NMR and carbon-13 nuclear magnetic resonance ¹³C-NMR). The corrosion inhibition effect of PMBH on mild steel in 1.0 M HCl was investigated using corrosion potential (E_CORR), potentiodynamic polarization, electrochemical impedance spectroscopy (EIS), and electrochemical frequency modulation (EFM) measurements. The obtained results indicated that PMBH has promising inhibitive effects on the corrosion of mild steel in 1.0 M HCl across all of the conditions examined. Scanning electron microscopy (SEM) was used to investigate the morphology of the mild steel before and after immersion in 1.0 M HCl solution containing 0.5 mM of PMBH. Surface analysis revealed improvement of corrosion resistance in presence of PMBH.